DS2 designer pre-fusion F vaccine induces strong and protective antibody response against RSV infection
Abstract DS-Cav1, SC-TM, and DS2 are distinct designer pre-fusion F proteins (pre-F) of respiratory syncytial virus (RSV) developed for vaccines. However, their immunogenicity has not been directly compared. In this study, we generated three recombinant vaccines using the chimpanzee adenovirus vecto...
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Nature Portfolio
2024-12-01
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Series: | npj Vaccines |
Online Access: | https://doi.org/10.1038/s41541-024-01059-9 |
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author | Yiling Yang Ruoke Wang Fenglin Guo Tian Zhao Yuqing Lei Qianqian Yang Yige Zeng Ziqing Yang Tatchapon Ajavavarakula Ruijie Tan Mingxi Li Haodi Dong Mengyue Niu Keyan Bao Hao Geng Qining Lv Qi Zhang Xuanling Shi Peng Liu Jiwan Ge Xinquan Wang Linqi Zhang |
author_facet | Yiling Yang Ruoke Wang Fenglin Guo Tian Zhao Yuqing Lei Qianqian Yang Yige Zeng Ziqing Yang Tatchapon Ajavavarakula Ruijie Tan Mingxi Li Haodi Dong Mengyue Niu Keyan Bao Hao Geng Qining Lv Qi Zhang Xuanling Shi Peng Liu Jiwan Ge Xinquan Wang Linqi Zhang |
author_sort | Yiling Yang |
collection | DOAJ |
description | Abstract DS-Cav1, SC-TM, and DS2 are distinct designer pre-fusion F proteins (pre-F) of respiratory syncytial virus (RSV) developed for vaccines. However, their immunogenicity has not been directly compared. In this study, we generated three recombinant vaccines using the chimpanzee adenovirus vector AdC68 to express DS-Cav1, SC-TM, and DS2. All three vaccines elicited robust serum binding and neutralizing antibodies following intramuscular priming and boosting. DS2 induced the strongest antibody responses, followed by SC-TM and DS-Cav1. DS2 also provided strong protection against live RSV challenge. Monoclonal antibodies (mAbs) isolated from long-lived antibody-secreting cells (ASCs) in the bone marrow six months post-immunization with AdC68-DS2 predominantly targeted site Ø as well as site II. One neutralizing antibody against site II, mAb60, conferred strong protection against live RSV infection in mice. These findings highlight the strong ability of the DS2 design in eliciting long-lived antibody responses and guide the development of next-generation RSV vaccines. |
format | Article |
id | doaj-art-5f42d64a55f1498f9768e4f979804c9a |
institution | Kabale University |
issn | 2059-0105 |
language | English |
publishDate | 2024-12-01 |
publisher | Nature Portfolio |
record_format | Article |
series | npj Vaccines |
spelling | doaj-art-5f42d64a55f1498f9768e4f979804c9a2025-01-05T12:08:00ZengNature Portfolionpj Vaccines2059-01052024-12-019111210.1038/s41541-024-01059-9DS2 designer pre-fusion F vaccine induces strong and protective antibody response against RSV infectionYiling Yang0Ruoke Wang1Fenglin Guo2Tian Zhao3Yuqing Lei4Qianqian Yang5Yige Zeng6Ziqing Yang7Tatchapon Ajavavarakula8Ruijie Tan9Mingxi Li10Haodi Dong11Mengyue Niu12Keyan Bao13Hao Geng14Qining Lv15Qi Zhang16Xuanling Shi17Peng Liu18Jiwan Ge19Xinquan Wang20Linqi Zhang21Comprehensive AIDS Research Center, Pandemic Research Alliance Unit, Center for Infection Biology, School of Basic Medical Sciences, Tsinghua UniversityComprehensive AIDS Research Center, Pandemic Research Alliance Unit, Center for Infection Biology, School of Basic Medical Sciences, Tsinghua UniversityThe Ministry of Education Key Laboratory of Protein Science, Beijing Frontier Research Center for Biological Structure, School of Life Sciences, Tsinghua UniversitySchool of Biomedical Engineering, Tsinghua UniversityComprehensive AIDS Research Center, Pandemic Research Alliance Unit, Center for Infection Biology, School of Basic Medical Sciences, Tsinghua UniversityComprehensive AIDS Research Center, Pandemic Research Alliance Unit, Center for Infection Biology, School of Basic Medical Sciences, Tsinghua UniversityComprehensive AIDS Research Center, Pandemic Research Alliance Unit, Center for Infection Biology, School of Basic Medical Sciences, Tsinghua UniversityComprehensive AIDS Research Center, Pandemic Research Alliance Unit, Center for Infection Biology, School of Basic Medical Sciences, Tsinghua UniversityComprehensive AIDS Research Center, Pandemic Research Alliance Unit, Center for Infection Biology, School of Basic Medical Sciences, Tsinghua UniversityComprehensive AIDS Research Center, Pandemic Research Alliance Unit, Center for Infection Biology, School of Basic Medical Sciences, Tsinghua UniversityComprehensive AIDS Research Center, Pandemic Research Alliance Unit, Center for Infection Biology, School of Basic Medical Sciences, Tsinghua UniversityComprehensive AIDS Research Center, Pandemic Research Alliance Unit, Center for Infection Biology, School of Basic Medical Sciences, Tsinghua UniversityComprehensive AIDS Research Center, Pandemic Research Alliance Unit, Center for Infection Biology, School of Basic Medical Sciences, Tsinghua UniversityComprehensive AIDS Research Center, Pandemic Research Alliance Unit, Center for Infection Biology, School of Basic Medical Sciences, Tsinghua UniversityComprehensive AIDS Research Center, Pandemic Research Alliance Unit, Center for Infection Biology, School of Basic Medical Sciences, Tsinghua UniversityComprehensive AIDS Research Center, Pandemic Research Alliance Unit, Center for Infection Biology, School of Basic Medical Sciences, Tsinghua UniversityComprehensive AIDS Research Center, Pandemic Research Alliance Unit, Center for Infection Biology, School of Basic Medical Sciences, Tsinghua UniversityComprehensive AIDS Research Center, Pandemic Research Alliance Unit, Center for Infection Biology, School of Basic Medical Sciences, Tsinghua UniversitySchool of Biomedical Engineering, Tsinghua UniversityState Key Laboratory of Respiratory Health and Multimorbidity, National Institute of Pathogen Biology, Chinese Academy of Medical Sciences & Peking Union Medical CollegeThe Ministry of Education Key Laboratory of Protein Science, Beijing Frontier Research Center for Biological Structure, School of Life Sciences, Tsinghua UniversityComprehensive AIDS Research Center, Pandemic Research Alliance Unit, Center for Infection Biology, School of Basic Medical Sciences, Tsinghua UniversityAbstract DS-Cav1, SC-TM, and DS2 are distinct designer pre-fusion F proteins (pre-F) of respiratory syncytial virus (RSV) developed for vaccines. However, their immunogenicity has not been directly compared. In this study, we generated three recombinant vaccines using the chimpanzee adenovirus vector AdC68 to express DS-Cav1, SC-TM, and DS2. All three vaccines elicited robust serum binding and neutralizing antibodies following intramuscular priming and boosting. DS2 induced the strongest antibody responses, followed by SC-TM and DS-Cav1. DS2 also provided strong protection against live RSV challenge. Monoclonal antibodies (mAbs) isolated from long-lived antibody-secreting cells (ASCs) in the bone marrow six months post-immunization with AdC68-DS2 predominantly targeted site Ø as well as site II. One neutralizing antibody against site II, mAb60, conferred strong protection against live RSV infection in mice. These findings highlight the strong ability of the DS2 design in eliciting long-lived antibody responses and guide the development of next-generation RSV vaccines.https://doi.org/10.1038/s41541-024-01059-9 |
spellingShingle | Yiling Yang Ruoke Wang Fenglin Guo Tian Zhao Yuqing Lei Qianqian Yang Yige Zeng Ziqing Yang Tatchapon Ajavavarakula Ruijie Tan Mingxi Li Haodi Dong Mengyue Niu Keyan Bao Hao Geng Qining Lv Qi Zhang Xuanling Shi Peng Liu Jiwan Ge Xinquan Wang Linqi Zhang DS2 designer pre-fusion F vaccine induces strong and protective antibody response against RSV infection npj Vaccines |
title | DS2 designer pre-fusion F vaccine induces strong and protective antibody response against RSV infection |
title_full | DS2 designer pre-fusion F vaccine induces strong and protective antibody response against RSV infection |
title_fullStr | DS2 designer pre-fusion F vaccine induces strong and protective antibody response against RSV infection |
title_full_unstemmed | DS2 designer pre-fusion F vaccine induces strong and protective antibody response against RSV infection |
title_short | DS2 designer pre-fusion F vaccine induces strong and protective antibody response against RSV infection |
title_sort | ds2 designer pre fusion f vaccine induces strong and protective antibody response against rsv infection |
url | https://doi.org/10.1038/s41541-024-01059-9 |
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